This article reports on a project that studied DNA samples from 45 populations for 63 SNPs in a region of 172kb across the region of 22q11.2 encompassing the COMT gene, focusing on 28 SNPs that span the COMT coding region and immediately flanking DNA.
Genetic variation at the Catechol-O-metyltransferase (COMT) gene has been significantly associated with risk for various neuropsychiatric conditions such as schizophrenia, panic disorder, bipolar disorders, anorexia nervosa, and others. It has also been associated with nicotine dependence, sensitivity to pain, and cognitive dysfunctions, especially in schizophrenia. The non-synonymous SNP in exon 4 - Val108/158Met - is the most studied SNP at COMT and the basis for most associations. It is not, however, the only variation in the gene; several haplotypes exist across the gene. Some studies indicate that the haplotypic combinations of alleles at the Val108/158Met SNP with those in the promoter region and in the 3' untranslated region are responsible for the associations with disorders and not the non-synonymous SNP by itself. The current study found that the haplotypes are from diverse evolutionary lineages that could harbor as yet undetected variants with functional consequences. Future association studies should be based on SNPs that define the common haplotypes in the population(s) being studied. 10 figures, 4 tables, and 39 references (publisher abstract modified)